Attenuation of Abnormal Scarring Using Spherical Nucleic Acids Targeting Transforming Growth Factor Beta 1

Adam Ponedal; Shengshuang Zhu; Anthony J. Sprangers; Xiao Qi Wang; David C. Yeo; Daniel C.S. Lio; Mengjia Zheng; Matthew Capek; Suguna P. Narayan; Brian Meckes; Amy S. Paller; Chenjie Xu; Chad A. Mirkin

doi:10.1021/acsabm.0c00990

Attenuation of Abnormal Scarring Using Spherical Nucleic Acids Targeting Transforming Growth Factor Beta 1

Adam Ponedal, Shengshuang Zhu, Anthony J. Sprangers, Xiao Qi Wang, David C. Yeo, Daniel C.S. Lio, Mengjia Zheng, Matthew Capek, Suguna P. Narayan, Brian Meckes, Amy S. Paller^*, Chenjie Xu^*, Chad A. Mirkin^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

Abnormal scarring is a consequence of dysregulation in the wound healing process, with limited options for effective and noninvasive therapies. Given the ability of spherical nucleic acids (SNAs) to penetrate skin and regulate gene expression within, we investigated whether gold-core SNAs (AuSNAs) and liposome-core SNAs (LSNAs) bearing antisense oligonucleotides targeting transforming growth factor beta 1 (TGF-β1) can function as a topical therapy for scarring. Importantly, both SNA constructs appreciably downregulated TGF-β1 protein expression in primary hypertrophic and keloid scar fibroblasts in vitro. In vivo, topically applied AuSNAs and LSNAs downregulated TGF-β1 protein expression levels and improved scar histology as determined by the scar elevation index. These data underscore the potential of SNAs as a localized, self-manageable treatment for skin-related diseases and disorders that are driven by increased gene expression.

Original language	English (US)
Pages (from-to)	8603-8610
Number of pages	8
Journal	ACS Applied Bio Materials
Volume	3
Issue number	12
DOIs	https://doi.org/10.1021/acsabm.0c00990
State	Published - Dec 21 2020

Funding

This material was supported by the NTU-NU Institute for NanoMedicine located at the International Institute for Nanotechnology, Northwestern University, U.S.A. and the Nanyang Technological University, Singapore. Research reported in this publication was also supported by the National Cancer Institute of the National Institutes of Health under award U54CA199091. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This material was also based on research sponsored by Air Force Research Laboratory under agreement FA8650-15-2-5518. The U.S. Government is authorized to reproduce and distribute reprints for Governmental purposes notwithstanding any copyright notation thereon. The views and conclusions contained herein are those of the authors and should not be interpreted as necessarily representing the official policies or endorsements, either expressed or implied, of Air Force Research Laboratory or the U.S. Government. A.P. is grateful for support from the National Science Foundation East Asia and Pacific Summer Institutes for U.S. Graduate Students (EAPSI) program. A.J.S. is grateful for support from a National Science Foundation Graduate Research Fellowship Program. B.M. is grateful for support from the Eden and Steven Romick Post-Doctoral Fellowship through the American Committee for the Weizmann Institute of Science. C.X. appreciates the start-up support from City University of Hong Kong (#9610472). Inductively coupled plasma measurements were conducted at the Northwestern University (NU) Quantitative Bioelemental Imaging Center (QBIC) MALDI-TOF mass spectrometry was conducted at the NU Integrated Molecular Structure Education and Research Center (IMSERC), which has received support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF EECS-1542205), the State of Illinois, and the International Institute for Nanotechnology (IIN). The TEM images made use of the BioCryo facility of Northwestern University’s NUANCE Center, which has received support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-1542205), the MRSEC program (NSF DMR-1720139) at the Materials Research Center, the International Institute for Nanotechnology (IIN), and the State of Illinois, through the IIN. It also made use of the CryoCluster equipment, which has received support from the MRI program (NSF DMR-1229693). Tissue sectioning and staining was conducted at the NU Skin Disease Research Center (SDRC) or the NU Mouse Histology and Phenotyping Laboratory (MHPL). These facilities were supported by the National Institutes of Health (NIAMS P30 AR057216), and the Robert H. Lurie Comprehensive Cancer Center (NCI P30-CA060553), respectively. Tissue sections were imaged at the NU Biological Imaging Facility (BIF), which has received support from the Chemistry for Life Processes Institute, the NU Office for Research and the Rice Foundation.

Keywords

TGF-beta
gene regulation
nanomedicine
scar
spherical nucleic acid
topical

ASJC Scopus subject areas

Biomaterials
General Chemistry
Biomedical Engineering
Biochemistry, medical

Access to Document

10.1021/acsabm.0c00990

Cite this

@article{824a4088041449aba9a07c3c63308074,

title = "Attenuation of Abnormal Scarring Using Spherical Nucleic Acids Targeting Transforming Growth Factor Beta 1",

abstract = "Abnormal scarring is a consequence of dysregulation in the wound healing process, with limited options for effective and noninvasive therapies. Given the ability of spherical nucleic acids (SNAs) to penetrate skin and regulate gene expression within, we investigated whether gold-core SNAs (AuSNAs) and liposome-core SNAs (LSNAs) bearing antisense oligonucleotides targeting transforming growth factor beta 1 (TGF-β1) can function as a topical therapy for scarring. Importantly, both SNA constructs appreciably downregulated TGF-β1 protein expression in primary hypertrophic and keloid scar fibroblasts in vitro. In vivo, topically applied AuSNAs and LSNAs downregulated TGF-β1 protein expression levels and improved scar histology as determined by the scar elevation index. These data underscore the potential of SNAs as a localized, self-manageable treatment for skin-related diseases and disorders that are driven by increased gene expression.",

keywords = "TGF-beta, gene regulation, nanomedicine, scar, spherical nucleic acid, topical",

author = "Adam Ponedal and Shengshuang Zhu and Sprangers, {Anthony J.} and Wang, {Xiao Qi} and Yeo, {David C.} and Lio, {Daniel C.S.} and Mengjia Zheng and Matthew Capek and Narayan, {Suguna P.} and Brian Meckes and Paller, {Amy S.} and Chenjie Xu and Mirkin, {Chad A.}",

note = "Publisher Copyright: {\textcopyright} ",

year = "2020",

month = dec,

day = "21",

doi = "10.1021/acsabm.0c00990",

language = "English (US)",

volume = "3",

pages = "8603--8610",

journal = "ACS Applied Bio Materials",

issn = "2576-6422",

publisher = "American Chemical Society",

number = "12",

}

TY - JOUR

T1 - Attenuation of Abnormal Scarring Using Spherical Nucleic Acids Targeting Transforming Growth Factor Beta 1

AU - Ponedal, Adam

AU - Zhu, Shengshuang

AU - Sprangers, Anthony J.

AU - Wang, Xiao Qi

AU - Yeo, David C.

AU - Lio, Daniel C.S.

AU - Zheng, Mengjia

AU - Capek, Matthew

AU - Narayan, Suguna P.

AU - Meckes, Brian

AU - Paller, Amy S.

AU - Xu, Chenjie

AU - Mirkin, Chad A.

N1 - Publisher Copyright: ©

PY - 2020/12/21

Y1 - 2020/12/21

N2 - Abnormal scarring is a consequence of dysregulation in the wound healing process, with limited options for effective and noninvasive therapies. Given the ability of spherical nucleic acids (SNAs) to penetrate skin and regulate gene expression within, we investigated whether gold-core SNAs (AuSNAs) and liposome-core SNAs (LSNAs) bearing antisense oligonucleotides targeting transforming growth factor beta 1 (TGF-β1) can function as a topical therapy for scarring. Importantly, both SNA constructs appreciably downregulated TGF-β1 protein expression in primary hypertrophic and keloid scar fibroblasts in vitro. In vivo, topically applied AuSNAs and LSNAs downregulated TGF-β1 protein expression levels and improved scar histology as determined by the scar elevation index. These data underscore the potential of SNAs as a localized, self-manageable treatment for skin-related diseases and disorders that are driven by increased gene expression.

AB - Abnormal scarring is a consequence of dysregulation in the wound healing process, with limited options for effective and noninvasive therapies. Given the ability of spherical nucleic acids (SNAs) to penetrate skin and regulate gene expression within, we investigated whether gold-core SNAs (AuSNAs) and liposome-core SNAs (LSNAs) bearing antisense oligonucleotides targeting transforming growth factor beta 1 (TGF-β1) can function as a topical therapy for scarring. Importantly, both SNA constructs appreciably downregulated TGF-β1 protein expression in primary hypertrophic and keloid scar fibroblasts in vitro. In vivo, topically applied AuSNAs and LSNAs downregulated TGF-β1 protein expression levels and improved scar histology as determined by the scar elevation index. These data underscore the potential of SNAs as a localized, self-manageable treatment for skin-related diseases and disorders that are driven by increased gene expression.

KW - TGF-beta

KW - gene regulation

KW - nanomedicine

KW - scar

KW - spherical nucleic acid

KW - topical

UR - http://www.scopus.com/inward/record.url?scp=85096672062&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85096672062&partnerID=8YFLogxK

U2 - 10.1021/acsabm.0c00990

DO - 10.1021/acsabm.0c00990

M3 - Article

C2 - 33709070

AN - SCOPUS:85096672062

SN - 2576-6422

VL - 3

SP - 8603

EP - 8610

JO - ACS Applied Bio Materials

JF - ACS Applied Bio Materials

IS - 12

ER -

Attenuation of Abnormal Scarring Using Spherical Nucleic Acids Targeting Transforming Growth Factor Beta 1

Abstract

Funding

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this